Females Live Longer than Males: Role of Oxidative Stress

Abstract

One of the most significant achievements of the twentieth century is the increase in human lifespan. In any period studied, females live longer than males. We showed that mitochondrial oxidative stress is higher in males than females and that the higher levels of estrogens in females protect them against ageing, by up-regulating the expression of antioxidant, longevity-related genes. The chemical structure of estradiol confers antioxidant properties to the molecule. However, the low concentration of estrogens in females makes it unlikely that they exhibit significant antioxidant capacity in the organism. Therefore we studied the mechanisms enabling estradiol to be antioxidant at physiological levels. Our results show that physiological concentrations of estrogens activate estrogen receptors and the MAPK and NFKB pathway. Activation of NFkB by estrogens subsequently activates the expression of Mn-SOD and GPx. Moreover, we have demonstrated that genistein, the most abundant phytoestrogen in soya, reproduces the antioxidant effect of estradiol at nutritionally relevant concentrations by the same mechanism, both in healthy ageing and in Alzheimer's disease. We conclude that estrogens and phytoestrogens up-regulate expression of antioxidant enzymes via the estrogen receptor and MAPK activation, which in turn activate the NFkB signalling pathway, resulting in the up-regulation of the expression of longevity-related genes.

Resveratrol affects differently rat liver and brain mitochondrial bioenergetics and oxidative stress in vitro: Investigation of the role of gender

“…The present work highlights the relevance of using mitochondrial-isolated fractions from male and female rats, which is very rare in the literature. Although we did not observe basal differences in mitochondrial preparations from both genders in most of the parameters investigated, except when measuring maximal respiration due to freezing/thawing cycles, it is known that estrogens have protective effects, enhancing antioxidant defenses and decreasing mitochondrial dysfunction (Borras et al, 2007;Eskes and Haanen, 2007;Vina et al, 2011). For instance, in liver mitochondrial the H 2 O 2 levels are lower in females than in males (Fig.…”

Sex‐Specific Genetic Variants are Associated With Coronary Endothelial Dysfunction

“…Errors in genes encoding inflammatory or anti‐inflammatory molecules are candidates for increasing risk of developing complications from coronary artery disease 36. There are sex‐specific variations in NF‐κB activity, which may play a role in development of CED and atherosclerosis 37, 38…”

Age-related changes in the activity and expression of manganese superoxide dismutase, and mitochondrial oxidant generation in female and male rats

“…Aging studies are mainly focused on gender-related differences in life span [10,[17][18][19][20]. Numerous studies have reported that females live significantly longer than males both in mammals and other vertebrates, as well as in some invertebrate species [18,[20][21][22].…”

“…Numerous studies have reported that females live significantly longer than males both in mammals and other vertebrates, as well as in some invertebrate species [18,[20][21][22].…”